Operational tolerance to skin allografts has been studied in mice and rats. Previous studies have shown that tolerant rats possess reactive lymphoid cells and serum blocking factors directed at allo-antigens of the tolerated graft. Studies undertaken within the last year have demonstrated that cytotoxic cells in tolerant rats are thymus-derived lymphocytes (manuscript submitted). Studies in the last year have also resulted in the development of assay systems to measure the primary response to allograft antigens in vitro. The optimal conditions for rat cell cultures have been defined (Manuscript submitted). The development of these systems will provide methods to better define the mechanism and site of serum blocking factors. Studies have also been undertaken to determine the genetic control of transplantation tolerance. Several strains of congenic mice, required for such experiments, have been obtained and are currently being bred. The objective of these studies remains to improve understanding of the cellular and humoral host mechanisms involved in the induction and maintenance of transplantation tolerance. The primary objective in the second year of the proposed grant will be to exploit the recently developed in vitro systems to allow for this analysis. BIBLIOGRAPHIC REFERENCES: Bernstein, I.D., and Wright, P.W.: Generation of cytotoxic lymphocytes in mixed leukocyte culture by rat lymphoid cells. Transplantation 21:173, 1976. Bernstein, I.D., Wright, P.W., and Cohen, E.: Generation of cytotoxic lymphocytes in vitro: Response of immune rat spleen cells to a syngeneic Gross virus-induced lymphoma in mixed lymphocyte-tumor culture. J. Immunol. 116:1367, 1976.